Specific binding of resiniferatoxin, an ultrapotent capsaicin analog, by dorsal root ganglion membranes

Abstract

We have previously demonstrated that resiniferatoxin (RTX), an unusual phorbol-related diterpene, induces similar responses in rodents to those induced by capsaicin, the pungent constituent of hot peppers (the genus Capsicum). Strikingly, RTX was 3-4 orders of magnitude more potent than was capsaicin. We report here specific binding of [3H]RTX to particulate preparations from dorsal root ganglia (DRG), a target tissue of both RTX and capsaicin action. The Kd was 0.27 nM for DRG from the rat; the Bmax was 160 fmol/mg. The respective values for pig DRG were 2.2 nM and 730 fmol/mg. Typical phorbol esters did not inhibit [3H]RTX binding. Capsaicin inhibited binding with 10(4)-fold lower affinity than RTX, consistent with the relative in vivo potencies. The specific [3H]RTX binding appears to represent the postulated capsaicin receptor.